Resource Center Journal Article Alert — August 29, 2008

Prepared by the National Sudden and Unexpected Infant/Child Death and Pregnancy Loss Resource Center at Georgetown University.

This journal article alert provides selected items added to the National Library of Medicine's PubMed database in the last week.

Past issues of Resource Center journal alerts are available at http://www.sidscenter.org.
Availability of full-text journal articles is often limited to subscribers or through inter-library loan. Please see your local library for copies of these articles, or view PubMed's How to Get the Journal Article for more details.

Sudden Infant Death

1. Gaudino JA Jr.
Progress Towards Narrowing Health Disparities: First Steps in Sorting Out Infant Mortality Trend Improvements Among American Indians and Alaska Natives (AI/ANs) in the Pacific Northwest, 1984-1997
Matern Child Health J. 2008 Aug 22. [Epub ahead of print]

Department of Public Health and Preventive Medicine, School of Medicine, Oregon Health and Sciences University, 2405 SW Stephenson St., Portland, OR, 97219, USA, james.a.gaudino@state.or.us.

Background Most AI/AN infant mortality rates (IMRs) remain higher than white rates. The Northwest Portland Area Indian Health Board (NPAIHB), serving 43 tribes, CDC and the Washington, Oregon, and Idaho health departments investigated AI/AN infant survival. Methods NPAIHB completed linking computerized birth certificate and birth-death files. We used death and birth cohorts, StatXact and SAS to compare 3-state resident, single and multi-year IMRs, basing infant race on mother's race, regardless of Hispanic origin. We used CDC's National Infant Mortality Surveillance ICD-9 categories for cause-specific rates. Results From 1984 to 1997, about 2100-2800 AI/AN births occurred annually. From 1984 to 1990, AI/AN IMRs were 1.8-2.4 fold higher than white rates. Then aggregate-year IMRs significantly declined from 16.3 in 1984-1987 to 6.7 in 1994-1997 (P < 0.0001), approaching the 5.6 1994-1997 white rate. In 1998 the AI/AN IMR rate increased to 10.3. AI/AN SIDS and respiratory distress syndrome rates decreased significantly, respectively, from 8.1 in between 1984-1987 to 2.3 in 1994-1996 and from 1.8 in 1984-1987 to 0.3 in 1991-1993, then leveled off. Significant rate declines occurred among most demographic, risk behavior, birthweight, gestational-age, reproductive risk, birth spacing, and labor/delivery sub-groups. Among others, AI/AN residents in Idaho as well as those who received no prenatal care and who had 0-5 month birth spacing experienced no improvements. Conclusions These uncommon rate declines imply multi-factorial improvements among Northwest AI/ANs. Community-level surveillance and interventions before conception through post-partum may further improve health. Collaborative efforts need to be maintained to continue to monitor changes in AI/AN infant health and maternal characteristics.

2. Yiallourou SR, Walker AM, Horne RS
Prone sleeping impairs circulatory control during sleep in healthy term infants: implications for SIDS
Sleep. 2008 Aug 1;31(8):1139-46

Ritchie Centre for Baby Health Research, Monash Institute of Medical Research, Monash University, Melbourne, Victoria, Australia.

STUDY OBJECTIVES: To determine the effects of sleeping position on development of circulatory control in infants over the first 6 months of postnatal age (PNA). DESIGN: Effects of sleeping position, sleep state and PNA on beat-beat heart rate (HR) and mean arterial pressure (MAP) responses to a head-up tilt (HUT) were assessed during sleep in infants at 2-4 wks, 2-3 mo and 5-6 mo PNA. MEASUREMENTS: Daytime polysomnography was performed on 20 full-term infants (12 F/8 M) and MAP was recorded continuously and noninvasively (Finometer). HUTs of 15 degrees were performed during active sleep (AS) and quiet sleep (QS) in both the prone and supine sleeping positions. MAP and HR data were expressed as the percentage change from baseline, and responses were divided into initial, middle and late phases. RESULTS: In the supine position HUT usually resulted in an initial increase (P < 0.05) in HR and MAP, followed by decreases (P < 0.05) in HR and MAP in the middle phase; subsequently HR and MAP returned to baseline in the late phase. By contrast, in the prone position the initial HUT-induced rises in HR and MAP were usually absent, and at 2-3 mo MAP actually decreased (P < 0.05); subsequently HR but not MAP returned to baseline. At 2-3 mo, MAP was lower (P < 0.05) in prone than supine sleeping throughout the HUT. CONCLUSIONS: Prone sleeping alters MAP responses to a HUT during QS at 2-3 mo PNA. Decreased autonomic responsiveness may contribute to the increased risk for SIDS of infants sleeping in the prone position.

Other Infant Death

1. Kvarnstrand L, Milsom I, Lekander T, Druid H, Jacobsson B
Maternal fatalities, fetal and neonatal deaths related to motor vehicle crashes during pregnancy: A national population-based study
Acta Obstet Gynecol Scand. 2008 Aug 11:1-7. [Epub ahead of print]

The Department of Obstetrics & Gynecology, Sahlgrenska Academy at Goteborg University, Goteborg, Sweden.

Objectives. Firstly, determine the mortality rate for: pregnant women; fetuses and neonates, due to motor vehicle crashes (MVCs) during pregnancy; and secondly, the rate of major injuries among pregnant women and the rate of involvement of pregnant women in crashes. Design. A national population-based, retrospective descriptive study. Setting. Sweden, 1991-2001. Population. All pregnant and non-pregnant women age 15-44. Methods. Linkage of national traffic, medical and autopsy registers. Main outcome measures. Maternal death or injury and corresponding fetal death. Results. MVCs during pregnancy caused 1.4 maternal fatalities per 100,000 pregnancies and a fetus/neonate mortality rate of least 3.7 per 100,000 pregnancies. The incidence of maternal major injury was 23/100,000 pregnancies and crash involvement was 207/100,000 pregnancies. Conclusions. MVCs during pregnancy were a significant cause of maternal fatalities, fetal and neonatal deaths, responsible for almost 1/3 of all maternal deaths and fatalities, and caused nearly three times more fetal plus neonatal deaths than maternal fatalities.

2. Picconi JL, Kruger M, Mari G
Ductus venosus S-wave/isovolumetric A-wave (SIA) index and A-wave reversed flow in severely premature growth-restricted fetuses
J Ultrasound Med. 2008 Sep;27(9):1283-9

Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan 48201, USA. jpicconi@med.wayne.edu

OBJECTIVE: Ductus venosus (DV) Doppler waveforms show 2 periods of decreased velocity during iso-volumetric relaxation (isovolumetric relaxation velocity [IRV]) and atrial contraction (A wave or end-diastolic velocity [EDV]). In intrauterine growth-restricted (IUGR) fetuses, both may become abnormal. The hypothesis for this study was that in severely premature IUGR fetuses, Doppler assessment of both the IRV and EDV allows a more accurate prediction of fetal outcome than absent/reversed end-diastolic flow (A/REDF) alone. METHODS: Ductus venosus Doppler waveforms were serially studied in 49 severely premature IUGR fetuses from diagnosis until death or delivery. The DV waveforms were assessed for peak systolic velocity (PSV), IRV, and EDV and qualitatively for forward end-diastolic flow or A/REDF. The S-wave/isovolumetric A-wave (SIA) index [PSV/(IRV + EDV)] for each fetus was compared to fetal/neonatal outcomes. RESULTS: There were 8 cases of fetal death (FD), 9 cases of neonatal death (ND), and 32 cases of neonatal survival (NS). A receiver operating characteristic (ROC) curve for the SIA index in all cases showed that values less than -1.25 correlated with FD and those greater than -1.25 correlated with live birth, with 100% sensitivity and 100% specificity. A second ROC curve of live births showed that values less than 2.07 correlated with NS and those greater than 2.07 correlated with ND with 67% sensitivity and 94% specificity. Ductus venosus A/REDF correlated with FD, ND, and NS with sensitivity values of 88%, 78%, and 32%, respectively. Of the 32 NSs, 11 (34%) had A/REDF with a median of 11 days before delivery. CONCLUSIONS: The SIA index is a novel Doppler parameter for assessment of severely premature IUGR fetuses that allows a much more accurate prediction of fetal outcome compared to A/REDF alone.

Miscarriage/Stillbirth/Prenatal Issues

1. Hauger MS, Gibbons L, Vik T, Belizan JM
Prepregnancy weight status and the risk of adverse pregnancy outcome
Acta Obstet Gynecol Scand. 2008 Aug 11:1-7. [Epub ahead of print]

Department of Community Medicine and General Practice, Medical Faculty, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

Objective. To examine the association between maternal pre-pregnancy weight status and the risk of stillbirth, pre-eclampsia and preterm delivery. Design. Hospital-based cohort study using prospectively recorded data. Setting. Ten public hospitals in Buenos Aires, Argentina. Population 46,964 pregnant women who had a delivery during 2003-2006. Methods. Prepregnancy body mass index (BMI) was used to categorize women in four weight categories from underweight to obese. The reference group were women with BMI between 18.5 and 24.9. Crude and adjusted odds ratios were calculated using multiple logistic regression analysis. Main Outcome: Preterm birth, pre-eclampsia and stillbirth. Results. The risk of preterm delivery decreased with increasing BMI, with the highest risk among underweight women (OR: 1.45; 95% CI: 1.26-1.67), and the lowest risk among the overweight. The risk of pre-eclampsia was highest among overweight (OR: 1.55; 95%CI: 1.30-1.86) and obese women (OR: 3.10; 95%CI: 2.54-3.78). Obese or overweight women did not have an increased risk of stillbirth in this study. Conclusions. Overweight and obese women have an increased risk for pre-eclampsia, while underweight women have an increased risk for preterm delivery. There is a high prevalence of overweight women in the obstetric population in Buenos Aires.

2. Strandberg-Larsen K, Tinggaard M, Nybo Andersen AM, Olsen J, Grønbæk M
Use of nicotine replacement therapy during pregnancy and stillbirth: a cohort study
BJOG. 2008 Aug 20. [Epub ahead of print]

National Institute of Public Health, University of Southern Denmark, Copenhagen K, Denmark.

Objective The objective of this study was to examine whether the use of nicotine replacement therapy (NRT) during pregnancy increases the risk of stillbirth. Design Cohort study with prospective data. Setting Denmark 1996-2002. Population A total of 87 032 singleton pregnancies enrolled in the Danish National Birth Cohort for which information on NRT use as well as smoking was available. Methods Outcome of pregnancy was identified by register linkage, with <1% loss to follow up. We conducted Cox regression analyses to estimate the hazard ratio (HR) and 95% CI of stillbirth according to the use of NRT, type of NRT use and a combination of NRT use and smoking. Main outcome measures Stillbirth, defined as delivery of a dead fetus after 20 completed weeks of gestation. Results A total of 495 pregnancies (5.7 in 1000 births) ended in stillbirth, 8 of which were among NRT users (4.2 in 1000 births). After adjustment for confounders, women who used NRT during pregnancy had a HR of 0.57 (95% CI 0.28-1.16) for stillbirth compared with those who did not use NRT. Smoking during pregnancy was associated with an increased risk of stillbirth (HR 1.46, 95% CI 1.17-1.82), while women who both smoked and used NRT had a HR of 0.83 (95% CI 0.34-2.00) compared with nonsmoking women who did not use NRT. Conclusion Our study does not indicate that use of NRT during pregnancy increases the risk of stillbirth.

3. Girardi G
Complement inhibition keeps mothers calm and avoids fetal rejection
Immunol Invest. 2008;37(5):645-59

Hospital for Special Surgery, Department of Medicine, Weill Medical College of Cornell University, NewYork, New York 10065, USA. girardig@hss.edu

The paternal antigens presented by the fetus could be considered foreign by the mother's immune system and elicit an immune response. Here we show that the complement system functions as an effector in fetal rejection in two different mouse models of pregnancy loss. In a mouse model of fetal loss and growth restriction (IUGR) induced by antiphospholipid antibodies (aPL), we found that complement activation is a crucial and early mediator of pregnancy loss. We demonstrated that C5a-C5aR interaction and neutrophils are key mediators of fetal injury. We identified tissue factor (TF) as a critical intermediate that, acting downstream of C5 activation, enhances neutrophil activity and trophoblast injury. In an antibody-independent mouse model of spontaneous miscarriage and IUGR (CBAxDBA) we also identified C5a as an essential mediator. Complement activation caused dysregulation of the angiogenic factors (deficiency of free vascular endothelial growth factor (VEGF) and elevated levels of soluble VEGF receptor 1) required for normal placental development. Inhibition of complement activation prevented angiogenesis failure and rescued pregnancies. Our studies in antibody-dependent and antibody-independent models of pregnancy complications identified complement activation as the crucial mediator of damage and will allow development of new interventions to prevent pregnancy loss and IUGR.

4. Mukri F, Bourne T, Bottomley C, Schoeb C, Kirk E, Papageorghiou AT
Evidence of early first-trimester growth restriction in pregnancies that subsequently end in miscarriage
BJOG. 2008 Sep;115(10):1273-8

Early Pregnancy, Gynaecological Ultrasound and MAS Unit, St George's Hospital, London, UK. faizah_mukri@hotmail.com

OBJECTIVES: To examine whether viable early pregnancies that subsequently end in miscarriage exhibit evidence of first-trimester growth restriction. DESIGN: Prospective cohort study. SETTING: Early pregnancy unit (EPU) of a teaching hospital. POPULATION: Women attending EPU between 5 and 10 weeks of gestation. METHODS: Women with spontaneously conceived intrauterine, viable singleton pregnancies with certain last menstrual period and regular cycles were included. The deviation between the observed and expected crown-rump length (CRL) for gestation was calculated and expressed as a z score. Pregnancies were followed up until the 11-14 week scan, and the deviation between those that remained viable and miscarried subsequently was calculated. MAIN OUTCOME MEASURES: Viability at 11-14 week scan. RESULTS: Over 6 months, 316 women met the inclusion criteria. Twenty-four (7.4%) women were excluded. Of the remaining 292, the pregnancy remained viable in 251 (86%) and 41 (14%) suffered a miscarriage. At the first transvaginal ultrasound, the z score of the mean measured CRL for pregnancies that remained viable was -0.82, SD 1.46, while in pregnancies that subsequently miscarried the z score was -2.42 and the CRL was significantly smaller, SD 1.31 (P < 0.0001). In the latter group, the initial CRL was below the expected mean for gestational age in all women, while in 61% (25/41), the CRL was at least 2 SDs below the expected mean. CONCLUSIONS: CRL was significantly smaller in pregnancies that subsequently ended in miscarriage. This suggests that early first-trimester growth restriction is associated with subsequent intrauterine death.

5. Syridou G, Spanakis N, Konstantinidou A, Piperaki ET, Kafetzis D, Patsouris E, Antsaklis A, Tsakris A
Detection of cytomegalovirus, parvovirus B19 and herpes simplex viruses in cases of intrauterine fetal death: Association with pathological findings
J Med Virol. 2008 Oct;80(10):1776-82

Department of Microbiology, Medical School, University of Athens, Athens, Greece.

There are previous indications that transplacental transmission of cytomegalovirus (CMV), parvovirus B19 (PB19) and herpes simplex virus types 1 and 2 (HSV-1/2) cause fetal infections, which may lead to fetal death. In a prospective case-control study we examined the incidence of these viruses in intrauterine fetal death and their association with fetal and placenta pathological findings. Molecular assays were performed on placenta tissue extracts of 62 fetal deaths and 35 controls for the detection of CMV, PB19 and HSV-1/2 genomes. Formalin-fixed, paraffin-embedded liver, spleen and placenta tissues of fetal death cases were evaluated histologically. Thirty-four percent of placental specimens taken from intrauterine fetal deaths were positive for any of the three viruses (16%, 13%, and 5% positive for CMV, PB19, and HSV-1/2, respectively), whereas only 6% of those taken from full term newborns were positive (P = 0.0017). No dual infection was observed. This difference was also observed when fetal deaths with a gestational age <20 weeks or a gestational age >20 weeks were compared with the controls (P = 0.025 and P = 0.0012, respectively). Intrauterine death and the control groups differed in the detection rate of CMV DNA (16% and 3%, respectively; P = 0.047), which was more pronounced in a gestational age >20 weeks (P = 0.03). Examination of the pathological findings among the PCR-positive and PCR-negative fetal deaths revealed that hydrops fetalis and chronic villitis were more common among the former group (P = 0.0003 and P = 0.0005, respectively). In conclusion, an association was detected between viral infection and fetal death, which was more pronounced in the advanced gestational age. Fetal hydrops and chronic villitis were evidently associated with viral DNA detection in cases of intrauterine death. J. Med. Virol. 80:1776-1782, 2008. (c) 2008 Wiley-Liss, Inc.

Prepared by the
National Sudden and Unexpected Infant/Child Death and Pregnancy Loss Resource Center
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